The Causal Relationships and Therapeutic Targets of Plasma Proteins in Ankylosing Spondylitis.

The purpose of this study was to assess the causal effects of circulating plasma proteins on ankylosing spondylitis (AS) and to explore potential therapeutic targets. The study used protein quantitative trait loci (pQTLs) for thousands of plasma proteins from nine genome-wide association studies (GWAS) as instrumental variables. The relationship between genetically predicted plasma proteins and AS was assessed through Mendelian randomization (MR) analysis.

Revision after knee arthroplasty due to Mycoplasma hominis infection: A case report and literature review.

Rationale: Mycoplasma hominis is an opportunistic pathogen commonly found in the human genitourinary system. However, infections caused by Mycoplasma hominis following knee arthroplasty are relatively rare.

Patient Concerns: A 68-year-old male patient underwent bilateral total knee arthroplasty 2 years ago due to osteoarthritis.

Uric acid to albumin ratio is a novel predictive marker for all-cause and cardiovascular death in diabetic patients: a prospective cohort study.

Background: Diabetes is one of the leading causes of death with an increasing prevalence worldwide. Diabetes-related premature mortality is largely preventable and reversible if identified and managed early. Accordingly, we intend to investigate the predictive value of uric acid to albumin ratio (UAR) for all-cause and cardiovascular death in diabetic patients.

Sex hormone imbalance and rheumatoid arthritis in American men: a cross-sectional analysis from NHANES 2011-2016.

Background: Emerging evidence suggests that sex hormones, particularly testosterone and sex hormone-binding globulin (SHBG), play a critical role in the pathophysiology of Rheumatoid arthritis (RA). However, the precise relationship between these hormonal factors and RA risk in men remains underexplored.

Methods: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016.

Causal relationships between air pollution and common autoimmune diseases: a two-sample Mendelian randomization study.

Air pollution is strongly associated with autoimmune diseases (ADs), however, the genetic causality between them remains poorly understood. Therefore, the aim of this study is to determine the relationship between common air pollutants and ADs through Mendelian randomization (MR) analysis. We conducted a MR study using aggregated data from publicly available genome-wide association studies (GWAS).

The antiarthritic effect of CBR-470-1 in hypoxic environment is to increase the level of NOD-like receptor family pyrin domain containing 3 ubiquitination by decreasing phosphoglycerate kinase 1 activity.

Background: Hypoxia can affect the occurrence and development of inflammation in humans, but its effects on the disease progression of osteoarthritis (OA) remain unclear. Synovial macrophages play an essential role in the progression of arthritis. Specifically, the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) in macrophages induces the secretion of a series of inflammatory factors, accelerating the progression of OA.

RUNX2 Phase Separation Mediates Long-Range Regulation Between Osteoporosis-Susceptibility Variant and XCR1 to Promote Osteoblast Differentiation.

GWASs have identified many loci associated with osteoporosis, but the underlying genetic regulatory mechanisms and the potential drug target need to be explored. Here, a new regulatory mechanism is found that a GWAS intergenic SNP (rs4683184) functions as an enhancer to influence the binding affinity of transcription factor RUNX2, whose phase separation can mediate the long-range chromatin interaction between enhancer and target gene XCR1 (a member of the GPCR family), leading to changes of XCR1 expression and osteoblast differentiation. Bone-targeting AAV of Xcr1 can improve bone formation in osteoporosis mice, suggesting that XCR1 can be a new susceptibility gene for osteoporosis.

Synovial transcriptome-wide association study implicates novel genes underlying rheumatoid arthritis risk.

Objectives: This study aimed to address the lack of gene expression regulation data in synovial tissues and to identify conditionally independent genes associated with rheumatoid arthritis (RA) in the synovium, a primary target tissue for RA.

Methods: Gene expression prediction models were built for synovial tissue using matched genotype and gene expression data from 202 subjects. Using this model, we conducted transcriptome-wide association study (TWAS), utilizing the largest RA genome-wide association study (GWAS) meta-analysis data (n = 276 020).

A landscape of gene expression regulation for synovium in arthritis.

The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition.

Relationship of weight change patterns from young to middle adulthood with incident rheumatoid arthritis and osteoarthritis: a retrospective cohort study.

Background: The relationship between weight change patterns and arthritis onset, specifically rheumatoid arthritis (RA) and osteoarthritis (OA), is unclear. We examined the association between weight changes from young adulthood to midlife and arthritis onset.

Methods: Using data from NHANES 1999-2018, participants with self-reported arthritis were selected.

EGFL6 activates the ERK signaling to improve angiogenesis and osteogenesis of BMSCs in patients with steroid-induced osteonecrosis of the femoral head.

Recently, epidermal growth factor-like domain protein 6 (EGFL6) was proposed as a candidate gene for coupling angiogenesis to osteogenesis during bone repair; however, the exact role and underlying mechanism are largely unknown. Here, using immunohistochemical and Western blotting analyses, we found that EGFL6 was downregulated in the femoral head tissue of patients with steroid-induced osteonecrosis of the femoral head (SONFH) compared to patients with traumatic femoral neck fracture (FNF), accompanied by significantly downregulation of osteogenic and angiogenic marker genes. Then, bone marrow mesenchymal stem cells (BMSCs) were isolated from the FNF and the SONFH patients, respectively, and after identification by immunofluorescence staining surface markers, the effect of EGFL6 on their abilities of osteogenic differentiation and angiogenesis was evaluated.

Emerging role and therapeutic implications of p53 in intervertebral disc degeneration.

Lower back pain (LBP) is a common degenerative musculoskeletal disease that imposes a huge economic burden on both individuals and society. With the aggravation of social aging, the incidence of LBP has increased globally. Intervertebral disc degeneration (IDD) is the primary cause of LBP.

Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) can be differentiated into osteoblasts and adipocytes. During these processes, super enhancers (SEs) play important roles. Here, we performed comprehensive characterization of the SEs changes associated with adipogenic and osteogenic differentiation of hMSCs, and revealed that SEs changed more dramatically compared with typical enhancers.

C1q/tumor necrosis factor-related protein 9 protects cultured chondrocytes from IL-1β-induced inflammatory injury by inhibiting NLRP3 inflammasome activation via the AdipoR1/AMPK axis.

C1q/tumor necrosis factor-related protein 9 (CTRP9) has been identified as a novel anti-inflammatory factor that participates in numerous pathological conditions. However, whether CTRP9 participates in the regulation of osteoarthritis has not been studied. This work sought to determine the possible role of CTRP9 in osteoarthritis using an in vitro model, namely interleukin-1β (IL-1β)-stimulated chondrocytes.

TRIM38 protects chondrocytes from IL-1β-induced apoptosis and degeneration via negatively modulating nuclear factor (NF)-κB signaling.

Tripartite motif protein 38 (TRIM38) has been documented as a vital modulator of inflammation. However, the relevance of TRIM38 in osteoarthritis is not yet known. In this work, we aimed to explore any possible effects of TRIM38 on interleukin-1β (IL-1β)-stimulated chondrocytes, an in vitro cellular model of osteoarthritis.

ABIN-1 protects chondrocytes from lipopolysaccharide-induced inflammatory injury through the inactivation of NF-κB signalling.

The A20-binding inhibitor of nuclear factor (NF)-κB-1 (ABIN-1) protein has recently been implicated as a key regulator of inflammation with involvement in multiple inflammatory diseases. However, the function of ABIN-1 in osteoarthritis (OA) remains unclear. In the current study, we explored the role of ABIN-1 in the regulation of lipopolysaccharide (LPS)-induced inflammatory injury of chondrocytes, which served as an in vitro model of OA.

LncRNA PART-1 targets TGFBR2/Smad3 to regulate cell viability and apoptosis of chondrocytes via acting as miR-590-3p sponge in osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease that commonly occurs in the elderly. This study focused on apoptosis and explored the modulating effects of long non-coding (lncRNAs) prostate androgen-regulated transcript-1 (PART-1) on chondrocytes apoptosis. In the present study, the PART-1 expression level was down-regulated in the OA cartilages.

miR-18a-5p promotes cell invasion and migration of osteosarcoma by directly targeting IRF2.

An increasing number of studies have suggested that microRNAs (miRNAs) are involved in the progress of many human cancers including osteosarcoma (OS). Especially, microRNA-18a-5p (miR-18a-5p) has been reported to associate with the occurrence, development and clinical outcomes of human cancers. Therefore, we investigated the functions of miR-18a-5p in OS.

A genome-wide pathway enrichment analysis identifies brain region related biological pathways associated with intelligence.

Intelligence is an important quantitative trait associated with human cognitive ability. The genetic basis of intelligence remains unclear now. Utilizing the latest chromosomal enhancer maps of brain regions, we explored brain region related biological pathways associated with intelligence.

Candidate methylated genes in osteoarthritis explored by bioinformatics analysis.

Background: This study aimed to explore potential novel genes correlated with osteoarthritis (OA).

Methods: The gene expression profile of GSE48422 was downloaded from the Gene Expression Omnibus (GEO) database. This dataset included five arthritic cartilage samples and five non-arthritic cartilage samples from five female OA patients.

Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats.

Rolipram, a phosphodiesterase-4 inhibitor, can activate the cyclic adenosine monophosphate (cAMP)/cAMP-responsive element binding protein (CREB) pathway to facilitate functional recovery following ischemic stroke. However, to date, the effects of rolipram on angiogenesis and cerebral ischemia-induced neuronal apoptosis are yet to be fully elucidated. In this study, the aim was to reveal the effect of rolipram on the angiogenesis and neuronal apoptosis following brain cerebral ischemia.